Mihara K, Kondo T, Suzuki A, Yasui N, Ono S, Otani K, Kaneko S
Department of Neuropsychiatry, Hirosaki University School of Medicine, 036-8562, Hirosaki, Japan.
Psychiatry Res. 2001 Feb 14;101(1):33-8. doi: 10.1016/s0165-1781(00)00247-x.
Previous studies have shown that subjects without Del alleles of the--141C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor (DRD2) gene have lower DRD2 density that those with one or two Del alleles. The present study aims to investigate the relationship between the -141C Ins/Del polymorphism and extrapyramidal adverse effects of bromperidol and nemonapride, antipsychotic drugs with a selective and potent DRD2 antagonistic property, in schizophrenic inpatients. Twenty-seven patients were treated with bromperidol at a fixed-dose of 6, 12 or 18 mg/day, and 25 patients were treated with nemonapride at a fixed-dose of 18 mg/day. The duration of treatment with these drugs was 3 weeks. The Ins and Del alleles were determined by PCR. Extrapyramidal adverse effects were assessed by the Udvalg for Kliniske Undersøgelser side effects rating scale. The subjects consisted of 38 homozygotes of the Ins allele and 14 heterozygotes of the Ins and Del alleles. There were no significant differences in the incidence or severity of extrapyramidal adverse effects between patients with and without the Del allele. It is possible that this result was due to a lack of statistical power. However, the present study suggests that the--141C Ins/Del polymorphism is not related to the development of extrapyramidal adverse effects during acute-phase treatment with antidopaminergic agents.
先前的研究表明,多巴胺D2受体(DRD2)基因启动子区域-141C Ins/Del多态性无Del等位基因的受试者,其DRD2密度低于有一个或两个Del等位基因的受试者。本研究旨在调查-141C Ins/Del多态性与溴哌利多和尼莫必利(具有选择性和强效DRD2拮抗特性的抗精神病药物)在精神分裂症住院患者中的锥体外系不良反应之间的关系。27例患者接受溴哌利多治疗,固定剂量为6、12或18mg/天,25例患者接受尼莫必利治疗,固定剂量为18mg/天。这些药物的治疗持续时间为3周。通过PCR确定Ins和Del等位基因。采用临床检查委员会副作用评定量表评估锥体外系不良反应。受试者包括38例Ins等位基因纯合子和14例Ins和Del等位基因杂合子。有Del等位基因和无Del等位基因的患者在锥体外系不良反应的发生率或严重程度上无显著差异。该结果可能归因于统计效力不足。然而,本研究表明,-141C Ins/Del多态性与抗多巴胺能药物急性期治疗期间锥体外系不良反应的发生无关。